Biomedical Engineering Reference
In-Depth Information
vided it had been applied over meshed autografts (Waymack et al. 2000). Further-
more, in a study of LSE in treatment of excisional wounds for skin cancer it was
concluded that treated defects resulted in more pliable and less vascular scar (Go-
hari et al. 2002). Treatment of patients with wounds resulting from excision of skin
cancers concluded that the LSE can safely be used in this patient population but it
was unclear whether use of LSE led to decreased healing times of acute wounds or
resulted in improved cosmetic outcome (Donohue et al. 2005). A study of acute full-
thickness defects in the lapine model concluded that a variant of LSE prepared with
a stratified epidermis significantly stimulated blood vessel formation and acceler-
ated epidermal wound closure significantly more than the variant prepared with a
monolayer epidermis (Ananta et al. 2012).
A number of clinical studies of the LSE and its commercial version, Apligraf
TM
,
have been directed toward the treatment of chronic skin wounds (Sabolinski et al.
1996; Falanga et al. 1998; Badiavas et al. 2002), and partial thickness skin wounds
(Hu et al. 2006). Details of these studies will not be described further as they deal
with injuries that lie outside the anatomical scope of this volume, i.e., the treatment
of anatomically well-defined defects (full-thickness skin defects).
A variant of the above protocol for preparation of the living skin equivalent was
developed, consisting of a collagenous graft that hypothetically simulated more
closely the distribution of collagen types in normal skin (Tinois et al. 1991). The
dermal substitute (DS) was a bilayer. It consisted of an upper (distal) layer of non-
porous type IV collagen and a bottom (proximal) layer of porous type I + III colla-
gens (average pore diameter, 50-100 μm); collagen in both layers had been cross-
linked following treatment with periodic acid. The DS was cultured in KC in vitro
until epidermal cell confluence was achieved. In culture, the epidermal layer was
multilayered, with desmosomes and a well-organized basal cell layer with tonofila-
ments. A thick, horny (keratinized) layer was observed when the culture was ex-
posed to air. The dermoepidermal junction formed in vitro was flat (no rete ridges);
it showed synthesis of hemidesmosome-like structures and an electron-dense band
resembling lamina densa. Following grafting on dermis-free defects in the athy-
mic mouse, the type IV collagen film was eventually degraded; well-differentiated
hemidesmosomes, an almost continuous lamina densa, and fibrils, reminiscent of
anchoring fibrils, were observed. A thick dermis was reported (Tinois et al. 1991).
An emphasis on inclusion of several additional macromolecular entities from
the extracellular matrix, than simply type I collagen and chondroitin sulfate (as in
DRT), led to the preparation of Matriderm™, a matrix comprising collagen types
I, III, and V, as well as hydrolysates of the fibrous protein elastin, normally present
in the dermis. This matrix has been used in combination with a split-thickness skin
autograft (STSG) to treat burn wounds, often to treat severe hand burns, where the
most desirable outcome is full range of motion, itself dependent largely on ease
of skin stretching (van Zuijlen et al. 2001; Ryssel et al. 2010). No difference in
scar elasticity could be observed when the combination Matriderm-SSTG was com-
pared with STSG grafted alone (Kolokythas et al. 2008). In another study, improved
range of motion of burned hands was observed when Matriderm™ was used with
STSG than when STSG was used alone (Ryssel et al. 2010). A comparative study
